This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The protein-conducting channel, more specifically known as the translocon (http://www.ks.uiuc.edu/Research/translocon/) or Sec complex, is an evolutionarily ancient protein complex that helps proteins cross or integrate into membranes (depending on whether they are soluble or membrane proteins). Present in all branches of life, the Sec complex is found in the cytoplasmic membrane in bacteria and archaea and in the membrane of the endoplasmic reticulum in eukaryotes. A passive channel, the Sec complex partners with other proteins that drive translocation of an unfolded polypeptide through the channel. In co-translational translocation, a common mode of translocation, this partner is the ribosome which feeds the nascent protein through the channel as it is synthesized. As a key step in protein targeting, translocation can be a deciding factor in the fate of proteins and even the cell as a whole. For example, poor recognition of the prion protein (PrP) leads to its abnormal aggregation and ultimately to lethal levels in the cell [1]. However, being able to enhance recognition and passage across the membrane could increase yields for artificially created proteins such as insulin [2]. In 2004, the Resource's collaborator, Tom Rapoport, released the first high resolution structure of the translocon. Obtained from Methanococcus jannaschii, this heterotrimeric membrane protein complex was resolved to 3.5 Angstroms. Based on this structure, specific details of translocation began to emerge. Observed structural elements were proposed to have specific functions, such as a constrictive pore ring and a plug blocking the exit of the channel. It was also proposed that a singular monomer within a dimeric or tetrameric complex serves as the active channel, leaving the role of oligomerization in question. Two dimeric forms of the channel with different functional behavior have been proposed (a 'back-to-back'and a 'front-to-front'dimer) although which is the in vivo state is unknown.